Bleeding is responsible for 30-40% of trauma-associated deaths and is the leading cause of death in the initial 6 hours after injury [Sauaia 1995]. The formation of a strong blood clot is necessary to staunch bleeding. However, blood clots in one-fourth of trauma patients are approximately 40% weaker [Davenport 2011] as a result of disrupted coagulation mechanisms and are therefore susceptible to rebleeding. Large-volume blood loss causes rapid depletion of available clotting factors. In addition, clotting factors are susceptible to dysfunction in the lower pH environment generated from lactic acid production as tissues become reliant on anaerobic respiration to compensate for limited oxygen delivery. Furthermore, hyperfibrinolysis, the accelerated enzymatic breakdown of the clot's supporting matrix, a proteinaceous fibrin fiber network, occurs [Raza 2013]. Reduced clot strength in patients with trauma-induced coagulopathy (TIC) is independently associated to a four-fold increase in 30-day mortality [Brohi 2003, Nystrup 2011].
Hemostasis by formation of a strong clot resistant to fibrinolysis is necessary to reverse coagulopathy and prevent downstream exsanguination and multi-organ failure. Since innate coagulation mechanisms are disabled, current approaches include transfusion of blood components for factor replacement and infusion of antifibrinolytic drugs to prevent clot breakdown. However, these methods have serious associated complications such as multi-organ failure and systemic inflammation and have limited ability to affect the multifactorial pathophysiology of TIC [Moore 1997]. An intravenously-administered hemostatic agent specifically designed to both bolster clot strength and reduce fibrinolysis at inaccessible internal bleeding sites without the aforementioned complications is thus needed. However, there are currently no such injectable hemostatic agents available.